RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration

Rousseau, Matthieu; Gaugler, Marie‐Hélène; Rodallec, Audrey; Bonnaud, Stéphanie; Pâris, François; Corre, Isabelle

doi:10.1016/j.bbrc.2011.09.150

Cited by 42 publications

(34 citation statements)

References 31 publications

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“…However, therapeutic doses of irradiation were shown to affect cell permeability of microvascular endothelial cells through Rho-mediated cytoskeleton remodeling (37). More recently, Rho-mediated focal adhesion and fibronectin adhesion were shown to be increased in endothelial cells in response to radiation (38). As Rho GTPases intervene in a number of additional cell pathways (e.g., cell cycle arrest, and regulation of apoptosis) (39), Rho GTPases potentially play a pivotal role in the cell response to simulated space conditions.…”

Section: The Rpm Has a Dominant Impact On Single Gene Expressionmentioning

confidence: 99%

Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Beck

Moreels

Quintens

et al. 2014

International Journal of Molecular Medicine

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Abstract. microgravity and cosmic rays as found in space are difficult to recreate on earth. However, ground-based models exist to simulate space flight experiments. In the present study, an experimental model was utilized to monitor gene expression changes in fetal skin fibroblasts of murine origin. Cells were continuously subjected for 65 h to a low dose (55 mSv) of ionizing radiation (IR), comprising a mixture of high-linear energy transfer (LET) neutrons and low-LET gamma-rays, and/or simulated microgravity using the random positioning machine (RPM), after which microarrays were performed. The data were analyzed both by gene set enrichment analysis (GSEA) and single gene analysis (SGA). Simulated microgravity affected fetal murine fibroblasts by inducing oxidative stress responsive genes. Three of these genes are targets of the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), which may play a role in the cell response to simulated microgravity. In addition, simulated gravity decreased the expression of genes involved in cytoskeleton remodeling, which may have been caused by the downregulation of the serum response factor (SRF), possibly through the Rho signaling pathway. Similarly, chronic exposure to low-dose IR caused the downregulation of genes involved in cytoskeleton remodeling, as well as in cell cycle regulation and DNA damage response pathways. Many of the genes or gene sets that were altered in the individual treatments (RPM or IR) were not altered in the combined treatment (RPM and IR), indicating a complex interaction between RPM and IR.

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Section: The Rpm Has a Dominant Impact On Single Gene Expressionmentioning

confidence: 99%

Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Beck

Moreels

Quintens

et al. 2014

International Journal of Molecular Medicine

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“…The cytoskeleton plays a major role in maintaining cell shape. Ionizing radiation has been clearly shown to alter cytoskeletal organization [68–70]. In vitro studies have highlighted different effects of radiation on the actin network, which vary depending on cell type and the dose delivered.…”

Section: Radiation-induced Plasma Membrane Signaling In the Endothelimentioning

confidence: 99%

“…In pulmonary microvascular endothelial cells, cytoskeletal disorganization with changes to actin filaments was observed following doses between 6 and 30 Gy [68,71]. In dermal microvascular cells, a dose of 15 to 20 Gy led to a rapid and persistent increase in stress fiber formation [69,70]. Actin structures are mainly reorganized through the action of specialized proteins, namely the Rho family of small GTPases, which includes RhoA, Rac and Cdc42 [72].…”

Section: Radiation-induced Plasma Membrane Signaling In the Endothelimentioning

confidence: 99%

Membrane Signaling Induced by High Doses of Ionizing Radiation in the Endothelial Compartment. Relevance in Radiation Toxicity

Corre

Guillonneau

Pâris

2013

IJMS

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Tumor areas can now be very precisely delimited thanks to technical progress in imaging and ballistics. This has also led to the development of novel radiotherapy protocols, delivering higher doses of ionizing radiation directly to cancer cells. Despite this, radiation toxicity in healthy tissue remains a major issue, particularly with dose-escalation in these new protocols. Acute and late tissue damage following irradiation have both been linked to the endothelium irrigating normal tissues. The molecular mechanisms involved in the endothelial response to high doses of radiation are associated with signaling from the plasma membrane, mainly via the acid sphingomyelinase/ceramide pathway. This review describes this signaling pathway and discusses the relevance of targeting endothelial signaling to protect healthy tissues from the deleterious effects of high doses of radiation.

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“…Acute effects of radiation on endothelial cells of different origin were documented with low, moderate and high doses of radiation (44)(45)(46)(47)(48)(49)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77). Similarly, convincing evidence of radiation-induced late effects due to endothelial cell damage has been reported (54,55,61).…”

Section: Endothelial Cell Responses To Radiationmentioning

confidence: 77%

Hemodynamic Flow-Induced Mechanotransduction Signaling Influences the Radiation Response of the Vascular Endothelium

et al. 2016

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RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration

Cited by 42 publications

References 31 publications

Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Membrane Signaling Induced by High Doses of Ionizing Radiation in the Endothelial Compartment. Relevance in Radiation Toxicity

Hemodynamic Flow-Induced Mechanotransduction Signaling Influences the Radiation Response of the Vascular Endothelium

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